AbstractEarly-life onset of high blood pressure is associated with the development of cardiovascular diseases in adulthood. In adolescents, limited evidence exists regarding the association between adherence to the Mediterranean Diet (MedDiet) and normal blood pressure (BP) levels, as well as its potential to modulate genetic predisposition to HTN. This study investigated the interaction between a MedDiet score and a recently developed HTN-genetic risk score (HTN-GRS) on blood pressure levels in a European adolescent cohort. The MedDiet score was derived from two non-consecutive 24-h dietary recalls and ranged from 0 (indicating low adherence) to 9 (indicating high adherence). Multiple linear regression models, adjusted for covariates, were employed to examine the relationship between the MedDiet score and BP z-scores and to assess the interaction effects between the MedDiet score and HTN-GRS on BP z-scores. MedDiet score showed a negative association with z-systolic BP (SBP) (ß = −0.40, p < 0.001) and z-diastolic BP (DBP) (ß = −0.29, p = 0.001). Additionally, a significant interaction effect was identified between the MedDiet score and HTN-GRS on z-SBP (ß = 0.02, p < 0.001) and z-DBP (ß = 0.02, p < 0.001). The modulatory effect of the MedDiet was more pronounced in females than in males, and HTN-GRS exhibited a stronger influence on DBP than on SBP.  Conclusion: The study suggests that higher adherence to the MedDiet is associated with reduced BP levels in adolescents and provides evidence of a genetic-diet interaction influencing BP in adolescents. What is Known:• Adherence to the Mediterranean diet may reduce BP levels. What is New:• It is the first study to assess the connection between adherence to a Mediterranean diet, a hypertension genetic risk score, and how they interact in influencing blood pressure.• It is conducted within a multicenter cohort of European adolescents.